1α,25-dihydroxyvitamin D3 regulates the expression of membrane-type matrix metalloproteinase-1 in normal human osteoblast-like cells

1α,25-dihydroxyvitamin D3 regulates the expression of membrane-type matrix metalloproteinase-1 in normal human osteoblast-like cells
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DOI:
10.1081/erc-120025042
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发表时间:
2003-01-01
期刊:
影响因子:
2.1
通讯作者:
Liao, EY
Liao, EY
中科院分区:
医学4区
文献类型:
--
作者:
Luo, XH;Liao, EY

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最近,膜型基质金属蛋白酶-1(MTI-MMP)被鉴定出来,发现它可以激活细胞膜上的proMMP-2,降解骨基质,参与骨形成。由于骨骼是 1alpha25-二羟基维生素 D-3 [1alpha25(OH)(2)D-3] 的靶组织,因此在本研究中,我们观察了 1alpha25(OH)(2)D-3 对正常人成骨样细胞 (hOB) 中 MTI-MMP 表达和 proMMP-2 激活的影响。 Western免疫印迹显示1alpha25(OH)(2)D-3时间和剂量依赖性地刺激MT1-MMF产生。通过ELISA,我们发现1alpha25(OH)(2)D-3增强了hOB培养物中proMMP-2的激活。我们的研究表明,la,25(OH)2D3部分通过上调MTI-MMP表达诱导MMP-2活化,并且由于MTI-MMP在骨代谢中发挥作用,hOB细胞中1alpha25(OH)(2)D-3诱导MTI-MMP水平可能有助于1alpha25(OH)(2)D-3促进骨形成和刺激骨吸收的新机制。
Recently, membrane-type matrix metalloprotemase-1 (MTI-MMP) was identified, and found that it can activate proMMP-2 on the cell membrane, degrade bone matrix, and participate in bone formation. Since bone is a target tissue of 1alpha25-dihydroxyvitamin D-3 [1alpha25(OH)(2)D-3], in the present study we observed the effects of 1alpha25(OH)(2)D-3 on MTI-MMP expression., and proMMP-2 activation in normal human osteoblast-like cells (hOB). Western immunoblots showed 1alpha25(OH)(2)D-3 time and dose dependently stimulated MT1-MMF production. By ELISA, we found that the activation of proMMP-2 in cultures of hOB was intensified by 1alpha25(OH)(2)D-3. Our studies suggest that la,25(OH)2D3 induces MMP-2 activation in part by up-regulating MTI-MMP expression, and since MTI-MMP plays a role in bone metabolism, the induction of MTI-MMP levels by 1alpha25(OH)(2)D-3 in hOB cells may contribute to a new mechanism by which 1alpha25(OH)(2)D-3 promotes bone formation and stimulates bone resorption.